TY - JOUR
T1 - Immunoglobulin-regulated expression of Borrelia burgdorferi outer surface protein A in vivo
AU - Hodzic, Emir
AU - Tunev, Stefan
AU - Feng, Sunlian
AU - Freet, Kim J.
AU - Barthold, Stephen W
PY - 2005/6
Y1 - 2005/6
N2 - Borrelia burgdorferi, the agent of Lyme disease, down-regulates outer surface protein A (OspA), which is abundantly expressed in ticks, during infection of the mammalian host. In this study we examined the signals that may be responsible for maintaining the OspA-negative state of spirochetes during infection. Transcription of ospA mRNA was found in tissues of C3H-severe combined immunodeficient (C3H-scid) mice, but not immunocompetent C3H mice, inoculated with cultured B. burgdorferi, tick-borne spirochetes, and host-adapted spirochetes. Transcription was more frequent at 4 weeks than at 1 week. Transcription was present at the host-tick interface as early as 24 h after tick attachment but declined at 48 and 72 h. Thus, ospA mRNA transcription in distant tissues and at later times in C3H-scid mice is probably due to up-regulation during infection. Adoptive lymphocyte transfer from naïve C3H mice to infected C3H-scid mice resulted in OspA seroconversion, confirming OspA expression in the host. Passive transfer of normal mouse serum, immunoglobulin M (IgM) from normal mouse serum, or IgG from normal mouse serum into infected C3H-scid mice resulted in down-regulation of ospA, but transfer of normal mouse serum depleted of immunoglobulin did not influence ospA mRNA transcription. Collectively, our results indicate that ospA mRNA transcription in the host is regulated by nonspecific immunoglobulin, which may be a natural antibody.
AB - Borrelia burgdorferi, the agent of Lyme disease, down-regulates outer surface protein A (OspA), which is abundantly expressed in ticks, during infection of the mammalian host. In this study we examined the signals that may be responsible for maintaining the OspA-negative state of spirochetes during infection. Transcription of ospA mRNA was found in tissues of C3H-severe combined immunodeficient (C3H-scid) mice, but not immunocompetent C3H mice, inoculated with cultured B. burgdorferi, tick-borne spirochetes, and host-adapted spirochetes. Transcription was more frequent at 4 weeks than at 1 week. Transcription was present at the host-tick interface as early as 24 h after tick attachment but declined at 48 and 72 h. Thus, ospA mRNA transcription in distant tissues and at later times in C3H-scid mice is probably due to up-regulation during infection. Adoptive lymphocyte transfer from naïve C3H mice to infected C3H-scid mice resulted in OspA seroconversion, confirming OspA expression in the host. Passive transfer of normal mouse serum, immunoglobulin M (IgM) from normal mouse serum, or IgG from normal mouse serum into infected C3H-scid mice resulted in down-regulation of ospA, but transfer of normal mouse serum depleted of immunoglobulin did not influence ospA mRNA transcription. Collectively, our results indicate that ospA mRNA transcription in the host is regulated by nonspecific immunoglobulin, which may be a natural antibody.
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U2 - 10.1128/IAI.73.6.3313-3321.2005
DO - 10.1128/IAI.73.6.3313-3321.2005
M3 - Article
C2 - 15908357
AN - SCOPUS:19744366674
VL - 73
SP - 3313
EP - 3321
JO - Infection and Immunity
JF - Infection and Immunity
SN - 0019-9567
IS - 6
ER -